P403: HIGH EXPRESSION OF STAT5 INDICATES POOR PROGNOSIS IN B CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Xiuli Xu, Zihong Cai, Zicong Huang, Yang Zhou, Haimei Liang, Qifa Liu, Hongsheng Zhou
Journal: HemaSphere (2023)

Background: Acute lymphoblastic leukemia(ALL) is increasingly recognized as a disease with significant genetic heterogeneity. The JAK-STAT signaling pathway is an intracellular mechanism stimulated by cytokine, which is involved in a series of physiological processes, including cell proliferation, differentiation, apoptosis, immunomodulation, etc. STAT5, as a crucial activated transcription factor, plays a critical role in transformation of progenitor B cells. The dysfunction of STAT5 can promote various tumorigenesis. The insight that JAK/STAT system activation is pervasive in B cell malignancies suggests novel therapeutic approaches. Aims: We conducted a study to explore the relationship between STAT5 expression and the prognosis of B-ALL, and may allow the refinement of risk stratification and treatment for this disease. Patients may benefit from risk stratification on the basis of STAT5 expression at diagnosis. Methods: We have examined a cohort of 184 ALL patients enrolled between January 2018 and December 2021 from Nanfang Hospital. STAT5 expression was detected by flow cytometry and its clinical effect was assessed by Kaplan-Meier curves. Prognostic factors for patient were estimated by Cox regression method. Results: A subgroup of 113 patients (61.1%) showed low STAT5 expression, whereas 71 patients (38.9%) displayed high STAT5 expression levels. The other clinical characteristics including gender, age and WBC counts were not significantly different between the two groups. High expression was significantly associated with longer overall survival, with a median survival in the high expression group of 3.13 years(95% CI: 1.49 to not reached) and was not reached for low expression group(p=0.0042). The median EFS was 0.857 years(95% CI, 0.717-2.257 years) in the high expression group compared with 4.32 years(95% CI: 2.15 to not reached). The same trends were found in cumulative incidence of relapse. Based upon data above, Accordingly, cytoplasmic STAT5 ex-pression may have prognostic implication. We evaluated the prognostic significance of STAT5 high expression group in PDT-ALL-2016. Prognostic factors were evaluated by univariate Cox regression. This method identified a survival benefit in patients with high cytoplasmic STAT5 expression (HR=2.01, p=0.005 in OS,HR=1.99,p＜0.001) in addition to other prognostic factors, including age, WBC, CNSL, immunophenotype, Ph positivity,karyotype,IKZF1deletion,CD20 expression, MRD1/2/3 and MRD remission. Multivariate analysis indicated that high STAT5 expression remained a significant prognostic factor with respect to overall survival (HR=2.07, p=0.014) while MRD remission remained significant(HR=0.45,p=0.012). Likewise, in the EFS analysis, only STAT5 expression and MRD remission remained significant predictors of EFS (HR=2.03,p=0.003;HR=0.47,p=0.005).These results suggest that changes in the STAT5 expression have independent prognostic significance and cannot be replaced by Ph positivity. Summary/Conclusion: Our results showed that high expression of STAT5 has been independently linked to poor prognosis in ALL. The detection of STAT5 phosphorylation could be introduced in the routine clinical workout for ALL patients.Keywords: Acute lymphoblastic leukemia, B cell acute lymphoblastic leukemia, STAT5, Prognosis